title: The positive association of obesity variants with adulthood adiposity strengthens over an 80-year period: a gene-by-birth year interaction.
abstract: OBJECTIVE
  To test the hypothesis that the statistical effect of obesity-related genetic variants on adulthood adiposity traits depends on birth year.
  
  
  METHODS
  The study sample included 907 related, non-Hispanic White participants in the Fels Longitudinal Study, born between 1901 and 1986, and aged 25-64.99 years (474 females; 433 males) at the time of measurement. All had both genotype data from which a genetic risk score (GRS) composed of 32 well-replicated obesity-related common single nucleotide polymorphisms was created, and phenotype data [including body mass index (BMI), waist circumference, and the sum of four subcutaneous skinfolds]. Maximum likelihood-based variance components analysis was used to estimate trait heritabilities, main effects of GRS and birth year, GRS-by-birth year interaction, sex, and age.
  
  
  RESULTS
  Positive GRS-by-birth year interaction effects were found for BMI (p < 0.001), waist circumference (p = 0.007), and skinfold thickness (p < 0.007). For example, each one-allele increase in GRS was estimated to result in a 0.16 increase in BMI among males born in 1930 compared to a 0.47 increase among those born in 1970.
  
  
  CONCLUSIONS
  These novel findings suggest the influence of common obesity susceptibility variants has increased during the obesity epidemic.
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minn., USA.
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Demerath
authors.forename: Audrey C
authors.initials: AC
authors.lastname: Choh
authors.forename: William
authors.initials: W
authors.lastname: Johnson
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: Miryoung
authors.initials: M
authors.lastname: Lee
authors.forename: Claire
authors.initials: C
authors.lastname: Bellis
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Czerwinski
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Bradford
authors.initials: B
authors.lastname: Towne
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000328:Adult; D015992:Body Mass Index; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009765:Obesity / Q000235:genetics*; D036801:Parturition / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019655:Quantitative Trait, Heritable; D055105:Waist Circumference / Q000235:genetics